Brief description of study

In the POPular CABG study we investigate if the addition of ticagrelor, a drug that inhibits
blood platelets from clotting, to treatment with aspirin will reduce the rate of saphenous
vein graft occlusion as assessed with coronary computed tomography angiography at 1 year
after coronary artery bypass grafting surgery.

Detailed Study Description

Rationale: Acetylsalicylic acid (ASA) is used to prevent the occlusion of grafts placed
during coronary artery bypass grafting surgery (CABG) and to reduce the incidence of
atherothrombotic events during follow-up. Graft occlusion occurs predominantly in saphenous
vein grafts (SVGs) and can result in symptoms of chest pain, myocardial infarction (MI) and
even death. The anti-thrombotic effect of ASA is a result of the inhibition of the generation
of thromboxane A2 (TXA2) in blood platelets. Despite ASA therapy, 6.8% to 26% of SVGs occlude
in the first year after CABG, mainly due to thrombus formation. This might be due to the fact
that ASA is not equally effective in all patients, indicated by a substantial amount of
patients that still generate TXA2 and show activated platelets, despite adequate ASA use. We
hypothesize that more potent platelet inhibition by the addition of ticagrelor to standard
ASA therapy could decrease the rate of SVG occlusion.

Main objective: To investigate whether a combination of ticagrelor 90mg twice daily and ASA
80mg once daily is superior to ASA 80mg once daily alone in the prevention of SVG occlusion
in patients who underwent CABG with use of one or more SVGs, as assessed with coronary
computed tomography angiography (CCTA) at 1 year after randomization.

Study design: Randomized, double-blind, placebo-controlled, multicenter trial. Number of
patients: Approximately 790 patients will be entered in the study, of whom a total of 720
patients will be randomized after surgery.

Study population: Patients undergoing isolated CABG with one or more SVGs.

Informed consent procedure, screening and sample size: We will screen patients and obtain
informed consent before CABG. After CABG patients who gave informed consent are screened
again to check if the patient fulfills the inclusion criteria and does not have any exclusion
criteria. A total of 720 patients will receive randomized study medication after CABG.

Intervention: Patients will be randomly assigned to treatment with 90mg of ticagrelor or a
matching placebo twice daily in addition to standard treatment with ASA for the duration of 1
year. Patients will be prescribed 80mg of ASA once daily according to routine clinical
practice. Graft patency will be assessed with CCTA 1 year after randomization. Platelet
function tests will be performed before surgery and 3 days and 1 year after randomization.
Thirty day and one-year follow-up of clinical events will be obtained for all patients by
screening the (electronic) patient file, telephonic interviews, study site visits and
possibly with questionnaires.